Limited hepatotoxic potential of acrylonitrile in rats

Abstract

The possible hepatotoxicity of acrylonitrile (ACN) was investigated based on reports of decreased hepatic glutathione in rats and liver abnormalities in man after exposure to ACN. Male and female rats pretreated po daily for 3 days with sodium phenobarbital (400 μmol/kg) or with Aroclor 1254 (300 μmol/kg) were given ACN (50, 75, 100, or 150 mg/kg) po for 1, 2, or 3 days, or 100 or 500 ppm ACN in drinking water for 21 days. Rats were killed 30 min or 24 hr after one dose of ACN or on Day 22 in the subacute study. Hepatic nonprotein sulfhydryl (NP-SH) concentration and the activities in serum of sorbitol dehydrogenase (SDH) and transminase (GPT) were measured. The liver was examined grossly and microscopically. Hepatic NP-SH decreased significantly (39, 60, 74, and 81%) at 30 min after 50, 75, 100, or 150 mg ACN, respectively. In some experiments serum SDH was significantly elevated (approximately fourfold) 24 hr after 150/mg/kg ACN. Pretreatment with phenobarbital and Aroclor 1254 resulted in only a slight enhancement of the ACN-induced elevation in serum SDH or GPT activities. Serum SDH increased 60% in rats given 500 ppm ACN in drinking water. Focal superficial necrosis of the liver associated ( p < 0.001) with hemorrhagic gastritis of a distended forestomach was found in rats necropsied 24 hr after administration of 150 mg/kg ACN. Other than this superficial necrosis, light microscopy revealed only minor changes in liver tissue. Electron microscopy disclosed no changes in the organelles of hepatocytes of rats treated for 21 days with ACN.